Antimicrobials and methods of making and using same
The present disclosure relates generally to the field of antimicrobial compounds and to methods of making and using them. These compounds are useful for treating, preventing, reducing the risk of, and delaying the onset of microbial infections in humans and animals. In some embodiments, the present disclosure provides a compound of Formula (I): or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer.
1. A compound of Formula (I)
or a tautomer or a pharmaceutically acceptable salt of the compound or tautomer, wherein:
R 1 is halo;
R 2 is halo;
R 3 is selected from, C 1-6 alkyl, NR c1 R d1 , NO 2 , OR a1 , SR a1 , S(O) 2 R b1 , and 5- to 6-membered heterocycloalkyl, wherein the C 1-6 alkyl is optionally substituted with a substituent selected from C(O)OR a1 , C(O)NR c1 R d1 , and C 1-4 alkoxy, and wherein the C 1-4 alkoxy is optionally substituted with C 1-4 alkoxy;
R 4 is selected from H, C 1-6 alkyl, and C 2-6 alkenyl, wherein the C 1-6 alkyl is optionally substituted with a substituent selected from OR a2 , SR a2 , NR c2 R d2 , and NR c2 C(=NR c2 )NR c2 R d2 ,
X is selected from 0, NR S , and CH 2 ;
R 5 is selected from H and C 1-4 alkyl;
W is selected from CR 6A R 6B and NR 6A ;
Y is N or CR 3 ;
R 6A is selected from H, C 1-6 alkyl, and C 1-6 haloalkyl;
R 6B is H; or
R 6A and R 6B together form an oxo group; or
R 6A and R 4 together with the carbon atom to which R 4 is attached, the W atom to which R 6A is attached and the X atom connecting W and the carbon atom to which R 4 is attached, form a 5- to 6-membered heterocycloalkyl ring containing 1-3 heteroatoms;
R 7 is selected from C 1-4 alkyl, C 1-4 haloalkyl, and C 3-5 cycloalkyl;
each of Ra a1 , R b1 , R c1 , R d1 , R a2 , R c2 , and R d2 is independently selected from H, C 1-4 alkyl, C 1-4 haloalkyl, and 5- to 6-membered heteroaryl; and
R 8 is selected from H, C 1-4 alkenyl, C 1-4 haloalkyl and C 1-4 alkyl optionally substituted with a substituent selected from amino, C 1-4 alkoxy, C 3-5 cycloalkyl, and 3- to 6-membered heterocycloalkyl;
R 9 is selected from H and halo; and
R e2 is selected from H and C 1-4 alkyl.
2. The compound of claim 1 , wherein R 1 is fluoro.
3. The compound of any one of claims 1 and 2 , wherein R 2 is chloro.
4. The compound of any one of claims 1 and 2 , wherein Y is CR 3 and R 3 is selected from, NO 2 , methylsulfonyl, methoxy, methylthio, carboxymethyl, methylaminocarbonylmethyl, N-morpholino, (2-methoxyethoxy)methyl, and dimethyl amino.
5. The compound of any one of claims 1 and 2 , wherein R 4 is selected from H, methyl, methylthiomethyl, hydroxymethyl, CH 2 NH(imidazol-2-yl), guanidinomethyl, ethenyl, CH 2 NH(pyridin-2-yl), and aminomethyl.
6. The compound of any one of claims 1 and 2 , wherein R 4 is H.
7. The compound of any one of claims 1 and 2 , wherein X is NR 5 .
8. The compound of any one of claims 1 and 2 , wherein X is O.
9. The compound of any one of claims 1 and 2 , wherein X is CH 2 .
10. The compound of any one of claims 1 and 2 , wherein W is CR 6A R 6B .
11. The compound of any one of claims 1 and 2 , wherein W is NR 6A .
12. The compound of any one of claims 1 and 2 , wherein R 6A is selected from H, methyl, trifluoromethyl, and difluoromethyl.
13. The compound of any one of claims 1 and 2 , wherein R 6A and R 6B together form an oxo group.
14. The compound of any one of claims 1 and 2 , wherein R 6A and R 4 together with the carbon atom to which R 4 is attached, the W atom to which R 6A is attached and the X atom connecting W and the carbon atom to which R 4 is attached, form a ring of any one of the following formulae:
15. The compound of any one of claims 1 and 2 , wherein R 6A and R 4 together with the carbon atom to which R 4 is attached, the W atom to which R 6A is attached and the X atom connecting W and the carbon atom to which R 4 is attached, form a ring of formula:
wherein x indicates a point of attachment to the ring containing Y.
16. The compound of any one of claims 1 and 2 , wherein R 7 is selected from methyl, trifluoromethyl, and cyclopropyl.
17. The compound of claim 1 , wherein R 9 is H.